Acute Viral Hepatitis.pptx...............

Acute viral hepatitis

1. Viral Hepatitis

2. Acute Viral Hepatitis

3. INTRODUCTION S ystemic infection affecting the liver predominantly. C aused by one of five viral agents : hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV).

4. Other transfusion-transmitted agents (e.g., "hepatitis G" virus and "TT" virus, have been identified but do not cause hepatitis). All these viruses are RNA viruses, except for hepatitis B, which is a DNA virus.

5. A ll types of viral hepatitis produce clinically similar illnesses. R ange from asymptomatic to fulminant and fatal infections and from subclinical persistent infections to rapidly progressive chronic liver disease with cirrhosis and even hepatocellular carcinoma.

6. Classified into two groups : - Enterically transmitted (HAV and HEV ) Parenterally transmitted (HBV, HCV and HDV ).

7. Enterically transmitted viruses N ot enveloped viruses, S hed in faeces , D o not cause chronicity D o not have prolonged viremia or carrier state. HAV and HEV are highly endemic in India.

8. HEV, a major cause of acute liver failure especially in pregnant women in India. In paediatric population, HAV is predominant cause of AVH.

9. Parenterally transmitted viruses HBV , HDV and HCV E nveloped viruses C an cause chronicity Can be associated with persistent viraemia and carrier state . About 15 % to 30% of acute cases in India are due to HBV infection . HDV infection is found in less than 10% patients with HBV infection .

10. Clinical features Majority of the AVH episodes are anicteric or subclinical; but when symptoms appear they are all similar in different types of AVH . C haracterised by prodrome of fever, anorexia, nausea , vomiting, mild abdominal pain, dark coloured urine followed by development of icterus . 5 to 10 times elevation in serum alanine transaminases ( ALT) with or without rise in serum bilirubin.

11. To determine the severity of AVH estimation of prothrombin time (PT) (expressed as INR) is essential. INR more than 1.5 is considered severe acute hepatitis. Majority of the AVH are self limiting. Chance of fulminant liver failure varies from 0.01% to 1%.

12. Hepatitis A

13. Virology and Modes of Transmission RNA virus belonging to Picorna family. N on enveloped, T ransmitted faeco - orally Incubation period of 15 to 50 days with an average of 30 days.

14. Epidemiology HAV has worldwide distribution and highly endemic in developing countries. India is hyperendemic region for HAV . There are estimated 1.5 million cases of HAV annually worldwide . Most of these cases occur in areas of poor hygiene and poor sanitation . Risk factors are children living in unhygienic condition, poor sanitation, consumers of high risk food , e.g. raw shell fish, people travelling to endemic areas.

15. Natural History and Clinical Course Main symptoms of HAV are fatigue, abdominal pain, anorexia, nausea , fever, dark coloured urine, jaundice, and diarrhoea . N ever causes chronic infection and produces life long immunity. R isk of fulminant hepatic failure (FHF) is 0.01% to 0.1% which increases with age and having pre-existing liver disease.

16. Diagnosis D iagnosed by serological tests. IgM anti-HAV suggests acute infection; HAV RNA can be detected in blood, stool and liver during early part of the illness, but this test is not used in clinical practice.

17. Treatment S ymptomatic and supportive measures ; N o specific antiviral treatment is required. Majority of the patients do not require hospital admission. Patients should be advised rest and given normal hygienic diet . Antiemetics may be given for nausea and vomiting.

18. Patients with severe AVH and patients with HAV super imposed on underlying chronic liver disease require hospitalization. A void hepatotoxic agents such as alcohol, oral contraceptive medicines, paracetamol and non-steroidal anti-inflammatory drugs.

19. Prevention Provision of clean drinking water, proper sewage disposal, public education about the hygiene. A ctive and passive immunisation are available . Pre-exposure prophylaxis with inactivated vaccines can give protection up to 20 years . Passive immunisation is used for postexposure prophylaxis within two weeks and should be accompanied with active vaccination.

20. Indication for active vaccination Travellers to high risk area Homosexual men Injection drug users Children and young adults when there is community outbreak. Susceptible patients with chronic liver disease Food handlers Children in the area of high endemicity

21. Schedule for hepatitis A vaccination Children over two years of age:- - 3 dose regime : Inactivated HAV vaccine (360 ELISA units) 0, 1 and 6 to 12 months - Two dose regime : Inactivated HAV vaccine (720 ELISA units) 0, 6 to 12 months

22. Adults above 19 years of age Inactivated HAV vaccine (1440 ELISA units) 0–6 to 12 months.

23. Post-exposure immunoprophylaxis 0.02 mL/kg body weight immunoglobulin specific to HAV on deltoid as early as possible after the exposure.

24. HEPATITIS B VIRUS (HBV)

25. Virology and Pathogenesis HBV is a single-stranded DNA virus , with particle size 22 to 42 nano micron with 3.2 kb circular DNA genome. HBV replicates through an RNA intermediate using a virus-encoded reverse transcriptase enzyme. HBV genome has four genes, namely: surface , core, DNA polymerase and X. Four antigens HBsAg , HBcAg , HBeAg and HBxAg that have been identified in relation to HBV. Antibodies against this can be detected in the blood and are useful in diagnosis of various phases of HBV infection.

26. There are at least 7 HBV genotypes (from A to G). Genotype D and A are more common in India . In immunocompetent persons , HBV is not cytopathic , and liver damage in this infection is caused through an immune-mediated mechanism directed against HBV-infected hepatocytes. However , in post-transplant patients , the virus appears to produce liver damage via a cytopathic effect.

27. Modes of Transmission Transmitted by blood-borne route, such as transfusion of infected blood and blood products, I ntravenous drug use, H aemodialysis , S exual contact, P ercutaneous exposure ( like needle-stick injuries, shared razor blades & tattooing , acupuncture, etc.), M other-to-newborn ( i.e. perinatal ) transmission.

28. Epidemiology G enerally seen in patients with high risk behaviour . More than one million people are infected annually . In India 15% to 30% of the acute hepatitis cases are due to HBV infection.

29. Natural History and Clinical Presentations Incubation period varies from 15 to 180 (average 60 to 90 ) days. In adults, almost 70% of acute infections are subclinical ; 30% develop icteric hepatitis . Perinatal or childhood HBV infections are usually asymptomatic . About 1% of patients with acute hepatitis B develop fulminant hepatic failure

30. HBV viraemia lasts for weeks to months after infection . Infection persisting beyond 6 months is labelled as chronic HBV. Risk of developing chronic HBV infection after acute exposure is dependent on age at the time of acquisition of infection.

31. Nearly 90% of neonates, around 50% of young children aged 1 to 5 years 1% to 5% of adults with acute HBV infection develop chronic infection and persistent viraemia . The risk of chronic HBV infection is higher among immunocompromised individuals like HIV-infected, patients under immunosuppressive therapy and haemodialysis patients.

32. Diagnosis B ased on detection of various antigens and antibodies in the serum, or of HBV-DNA in serum or liver tissue . Presence of HBsAg in the blood suggests the presence of HBV infection. Presence of HBeAg in blood suggests active viral replication . IgM anti- HBc antibodies indicate recent (acute) infection .

33. Anti-HBs antibodies appear with the clearance of HBV infection, and their presence suggests complete recovery. Detecting the presence and quantity of HBV-DNA in blood by polymerase chain reaction is useful in assessing whether virus is actively replicating , judging the need for and response to treatment.

34. Treatment In adults is mostly a self-limiting disease and hence does not require any specific anti-viral treatment. The patients should be followed up to detect those in whom the infection becomes chronic ; this is particularly important for children . Treatment with oral antivirals like Lamivudine, Telbivudine or Entecavir is indicated in patients with fulminant HBV , protracted severe HBV infection in immunosuppressed patients .

35. Prevention S creening the transfused blood and blood products for HBsAg , Using disposable needles and syringes, using safety precautions P racticing safe sex. Active and passive immunisation .

36. Indication for active vaccination Universal infant immunisation shortly after the birth High risk groups Household contacts of HBV carriers Health care professionals

37. Injection drug abusers Homosexual men Individual with multiple sex partners Haemodialysis patients Patients with chronic liver disease

38. HBV vaccine schedule Below the age of 19 years 10mu IM on deltoid at 0, 1, 6 months Above the age of 19 years 20 mu intramuscularly on deltoid at 0, 1 , 6 months Post exposure prophylaxis 0.04 – 0.07 mL/kg HBIG intramuscularly within 48 hours along with the first dose of active vaccine . Further doses of active vaccine at 1 and 6 months should be continued.

39. In neonates born to HBsAg positive mothers should be vaccinated at a dose of 0.5 ml of HBIG within 12 hours of birth along with the first dose of active vaccination. Futher doses of active vaccine at 1 and 6 months should be continued.

40. HEPATITIS C VIRUS (HCV)

41. Virology and Pathogenesis S ingle-stranded , enveloped RNA virus with a single open reading frame and 9.5 kb linear RNA genome. The viral strains have significant genetic variability and have been grouped into six genotypes . In India, genotype 3 is the commonest; it is characterized by a good response to interferon treatment.

42. The exact mechanism of hepatocellular injury in HCV infection is unknown. Initially , HCV-induced liver injury was considered to be cytopathic in nature but current data suggest that host immune responses to HCV-infected hepatocytes play a major role in the pathogenesis of chronic hepatitis C.

43. Mode of Transmission Similar to HBV infection, HCV is also transmitted by blood-borne routes . Transmissibility of HCV is much lower than that of HBV. Recipients of infected blood and blood products, intravenous drug abusers, and haemodialysis patients form the major HCV risk groups. Sexual and perinatal transmission of HCV is uncommon .

44. Epidemiology Worldwide prevalence of HCV infection is around 1 %. C arrier rate in India is around 1% to 2 %. R esponsible for 20% to 30 % of patients with chronic liver disease in India.

45. Natural History and Clinical Presentation Incubation period of HCV ranges from 15 to 160 days . Prolonged viremia and persistent infection are common. More than 75% of acute HCV infections are silent. Only 25% acute HCV infections manifest as clinical hepatitis.

46. Nearly 50% to 85 % of patients with HCV infection develop chronic infection; of these, 60% to 70% develop chronic hepatitis, 30% develop cirrhosis and 15% develop hepatocellular carcinoma. Average time duration between acquisition of infection and development of chronic hepatitis, cirrhosis and HCC is 10 years, 20 to 30 years and 40 years, respectively.

47. Diagnosis Diagnosis of HCV infection depends on detection of anti-HCV antibodies , using enzyme immunoassays (EIAs ). In acute HCV infection serum HCV RNA are detected within 1 to 2 weeks of exposure while elevation in ALT occurs 2 to 8 weeks after exposure. Anti HCV antibody develop 4 to 6 weeks after exposure to hepatitis C.

48. Treatment More than 50% patients with acute HCV infection develop chronicity . Treatment of acute HCV infection after 12 weeks is recommended as spontaneous resolution is unlikely . Interferon alpha, peg interferon alpha and peg interferon alpha + ribavirin have been shown to be highly effective.

49. Prevention Use of blood from voluntary blood donors (as opposed to professional donors) and screening of blood and blood products using an anti-HCV antibody test prior to blood transfusion. Use of disposable syringe and needles. N o active or passive immunisation is available for prevention.

50. HEPATITIS D INFECTION (HDV)

51. HDV is an incomplete enveloped virus with particle size of 35- 37 nano microns, 1.7 kb circular RNA genome . It uses HBsAg of HBV as its envelope protein , and hence can cause infection only in the presence of HBV infection. Infection with both HDV and HBV may be acquired simultaneously (known as deltacoinfection ); alternatively , HDV infection may occur in a person previously having chronic HBV infection ( delta- superinfection ).

52. T ransmitted by parenteral and sexual routes; vertical transmission is extremely rare. P revalent worldwide. However, its frequency has shown a decline globally, as well as in India.

53. HDV coinfection has a good prognosis with 80% to 90% of patients showing complete recovery. Fulminant hepatic failure is seen in 5% to 10% of patients as compared to only 1% of those with isolated acute HBV infection. HDV superinfection is associated with increased rates of progression to cirrhosis, decompensation , development of hepatocellular carcinoma and death as compared to isolated chronic HBV infection. Clinical presentation varies from asymptomatic carrier stage, acute hepatitis, fulminant hepatitis , chronic hepatitis, cirrhosis decompensation and HCC.

54. Acute deterioration in chronic stable HBV infection should lead to suspicion of delta superinfection . Diagnosis depends on demonstration of anti-HDV antibodies in the serum and HDV-RNA in serum or liver tissue.

55. Response to interferon as well as lamivudine is suboptimal. Since HDV depends on HBV for survival and multiplication , it can be prevented using methods to prevent the latter.

56. HEPATITIS E VIRUS (HEV)

57. Virology and Modes of Transmission P ositive stranded 7.6 kb base N on enveloped RNA virus and belongs to family of calcivirus . Particle size of 32 to 34 nano microns. P redominantly transmitted by faeco -oral route. I ncubation period of 2 to 9 weeks with mean of 6 weeks.

58. Epidemiology C ommon cause of acute sporadic and epidemic viral hepatitis in India. Contamination of drinking water due to sewage has been the important source of majority of these epidemics. Faecal contamination may be due to backflow during the floods , leaking sewers located close to the corroded drinking water pipes and contamination of well water during raining seasons.

59. Natural History and Clinical Course Clinical manifestation ranges from asymptomatic to icteric hepatitis to fulminant hepatic failure (FHF). Prodromal symptoms are similar to other forms of AVH. Cholestatic hepatitis with jaundice and itching may last for several months in 20% to 30% patients. Mostly self-limiting acute infection. 1 % of the patients with HEV can develop FHF. Pregnant females (especially during 2nd and 3rd trimester) have high attack rates and 10% to 12% chance of FHF.

60. Diagnosis IgM anti HEV antibodies for diagnosing of acute HEV infection.

61. Treatment S upportive.

62. Chronic Viral Hepatitis

63. D efined as hepatic necro -inflammation continuing for more than 6 months. U sually progresses to fibrosis and subsequent architectural distortion with regenerating nodules leading to cirrhosis. C auses of chronic hepatitis which can be broadly categorized into viral and non-viral causes.

64. Viral Chronic hepatitis B Chronic hepatitis C Chronic hepatitis D

65. Non-Viral Alcoholic hepatitis Non-alcoholic steatohepatitis Wilson’s disease Drugs Auto-immune hepatitis

66. Hepatitis B Virus (HBV)

67. Epidemiology Hepatitis B is endemic throughout the world especially in countries like Bangladesh , Thailand and Myanmar which have HBsAg carrier rates as high as 9 to 12%. In India, the carrier rate has been found to be around 4 to 7% with an estimated 45 million infected individuals.

68. Clinical features and outcome U sually asymptomatic and is commonly detected on routine blood testing or during evaluation of incidental , unexplained elevation in alanine aminotransferase (ALT) levels. W hen present, are generally mild and non-specific such as fatigue, mild right upper quadrant pain , nausea, weight loss, weakness, pruritus , etc. Patients with more advanced disease may have jaundice, abdominal swelling, gastrointestinal (GI) bleed or hepatic encephalopathy.

69. Sometimes, the condition is diagnosed when the patient presents with an acute hepatitis illness which is due to reactivation of chronic hepatitis B. Physical examination is usually unremarkable but stigmata of chronic liver disease may be present. Hepatomegaly with or without splenomegaly may be present depending on the stage of disease.

70. Outcome of chronic HBV Most patients are infected in early childhood and initial infection leads to HBeAg -positive disease with high-level viraemia and minimal liver damage ( immune tolerant phase ). With advancing age, many develop an immune response ( immune clearance phase ) that leads to liver inflammation with progressive disease (high AST/ ALT levels) and often seroconversion to HBeAg -negative phase of infection with low-level viraemia and normal liver function tests (LFT) ( inactive replicative phase ). A proportion of patients have reactivation of infection ( reactivation phase ) and develop HBeAg negative disease with fibrosis progression.

71. Diagnosis Patients with chronic hepatitis B (CHB) are diagnosed when hepatitis B surface antigen ( HBsAg ) persists in serum for more than 6 months.

72. Hepatitis B core antibody is present in CHB infection and presence of HBeAg or high HBV-DNA are markers of replicative virus. T ransaminases (AST, ALT) are typically elevated usually 1 to 5 times the upper limit of normal with ALT > AST. A lkaline phosphatase level is only mildly elevated . I n advanced stages of disease where reversal of A:G ratio may be seen .

73. Abdominal ultrasonography (USG) is the most commonly used imaging modality although it is not useful in making the diagnosis . Its importance, however, lies in distinguishing patients with cirrhosis (small, shrunken nodular liver or atrophy of right lobe with hypertrophy of caudate/left lobe) or those with portal hypertension. It is also a useful screening test for hepato -cellular carcinoma . ( USG) elastography ( fibroscan ) is a new non-invasive imaging modality used for assessment of fibrosis in chronic hepatitis.

74. Liver biopsy is not required for diagnosis of chronic viral hepatitis . Its usefulness lies in the histological assessment of liver for severity of necro -inflammation (grading) and degree of fibrosis (staging ).

75. Treatment Treatment is restricted to patients with active inflammation and high replicative state ( HBeAg positive or high level HBV-DNA). Such patients have higher risk of progressive disease leading to cirrhosis and hepato -cellular carcinoma.

76. Current guidelines advocate treatment in patients with HBV-DNA >20,000μ/ml in HBeAg -positive patients . HBV-DNA >2000μ/ml in HBeAg -negative patients .

77. S hort-term goal of treatment is to convert patients from the high replication phase ( HBeAg -positive or high HBV-DNA) to the low replication phase characterized by the appearance of HBeAb (called as seroconversion ) or disappearance of HBV-DNA . L ong-term goals are to delay or prevent histological progression to cirrhosis and hepato -cellular carcinoma.

78. Treatment options include interferon injections (both standard and pegylated ) and anti-viral drugs, such as nucleoside or nucleotide inhibitors. Currently used oral anti-viral drugs include lamivudine , adefovir , entecavir and tenofovir . Interferon therapy is of finite duration, whereas a long-term therapy should be planned when using nucleoside analogues .

79. Usual regimen for Peg-interferon is a weekly dose for 12 months . Nucleoside treatment should be continued for at least 6 months after seroconversion in HBeAg -positive patients, or after HBV DNA levels have become undetectable in HBeAg -negative patients. Interferons should be avoided in HBeAg -negative patients as the results are disappointing.

80. Hepatitis C Virus

81. Clinical features Acute infection with hepatitis C leads to chronicity in almost 85 % of the patients. Chronic infection leads to a slowly progressive hepatitis that can cause significant liver disease including cirrhosis and sometimes hepato -cellular carcinoma over 15 to 30 years. The disease is usually asymptomatic and detected during routine testing or during evaluation for asymptomatic elevation of transaminases.

82. Diagnosis D iagnosis is based on the presence of both anti-HCV and HCV-RNA . P attern of LFT abnormality, use of imaging modalities and assessment of liver histology in chronic hepatitis C is similar to that in chronic hepatitis B.

83. Treatment All anti-HCV positive patients with detectable HCV-RNA are potential candidates for treatment. O ptimal therapy is the combination of peginterferon alfa and ribavirin. Genotype 1 and 4 patients are treated with 48 weeks of treatment while genotype 2 and 3 patients are treated with 24 weeks of treatment. The expected response rate is lower with genotype 1 and 4 patients (55 to 60%) compared to genotype 2 and 3 (75 to 80%).